Gene regulatory networks in cardiac conduction system development.
Gene regulatory networks in cardiac conduction system development.
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DOI：
10.1161/circresaha.111.260026
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发表时间：
2012-05-25
影响因子：
20.1
通讯作者：
Munshi NV
中科院分区：
文献类型：
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作者：
Munshi NV
心脏传导系统是一个专门的心肌细胞束，负责维持正常的心律。鉴于其在协调心脏功能中的关键作用，对传导系统形成的分子机制的详细分析将有助于我们对心律失常病理生理学的理解，并影响新的治疗策略的发展。从历史上看，区分传导系统细胞与邻近工作的肌细胞的能力是进行全面机制研究的主要技术挑战。早期的谱系追踪实验表明，传导细胞来源于心肌细胞的前体，这些说法已经通过使用更现代的方法得到证实。然而，传导细胞的区域特化给这个系统增加了额外的复杂性，似乎传导系统的不同组成部分利用独特的发育形成模式。许多转录因子及其下游靶基因参与传导系统的区域分化的鉴定提供了如何实现谱系承诺的见解。此外，通过采用尖端的遗传技术与复杂的表型能力相结合，研究人员在描述协调传导系统形成的调控网络及其在心律和生理中的作用方面取得了实质性进展。本文综述了这些基因调控网络在心脏传导系统发育中的连通性，并讨论了它们如何为理解正常和病理人类心律提供基础。
The cardiac conduction system is a specialized tract of myocardial cells responsible for maintaining normal cardiac rhythm. Given its critical role in coordinating cardiac performance, a detailed analysis of the molecular mechanisms underlying conduction system formation should inform our understanding of arrhythmia pathophysiology and affect the development of novel therapeutic strategies. Historically, the ability to distinguish cells of the conduction system from neighboring working myocytes presented a major technical challenge for performing comprehensive mechanistic studies. Early lineage tracing experiments suggested that conduction cells derive from cardiomyocyte precursors, and these claims have been substantiated by using more contemporary approaches. However, regional specialization of conduction cells adds an additional layer of complexity to this system, and it appears that different components of the conduction system utilize unique modes of developmental formation. The identification of numerous transcription factors and their downstream target genes involved in regional differentiation of the conduction system has provided insight into how lineage commitment is achieved. Furthermore, by adopting cutting-edge genetic techniques in combination with sophisticated phenotyping capabilities, investigators have made substantial progress in delineating the regulatory networks that orchestrate conduction system formation and their role in cardiac rhythm and physiology. This review describes the connectivity of these gene regulatory networks in cardiac conduction system development and discusses how they provide a foundation for understanding normal and pathological human cardiac rhythms.